United States
Environmental Protection
1=1 m m Agency
EPA/690/R-02/01 IF
Final
9-25-2002
Provisional Peer Reviewed Toxicity Values for
Mercuric sulfide
(CASRN 1344-48-5)
Derivation of a Chronic Oral RfD
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

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Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
i.v.	intravenous
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
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MTD
maximum tolerated dose
MTL
median threshold limit
NAAQS
National Ambient Air Quality Standards
NOAEL
no-observed-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-observed-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
PBPK
physiologically based pharmacokinetic
PPb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor
Hg
microgram
|j,mol
micromoles
voc
volatile organic compound
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PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
MERCURIC SULFIDE (CASRN 1344-48-5)
Derivation of a Chronic Oral RfD
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3.	Other (peer-reviewed) toxicity values, including:
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because science and available information evolve, PPRTVs are initially derived with a
three-year life-cycle. However, EPA Regions or the EPA Headquarters Superfund Program
sometimes request that a frequently used PPRTV be reassessed. Once an IRIS value for a
specific chemical becomes available for Agency review, the analogous PPRTV for that same
chemical is retired. It should also be noted that some PPRTV manuscripts conclude that a
PPRTV cannot be derived based on inadequate data.
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Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
An RfD for mercuric sulfide (HgS) is not available on IRIS (U.S. EPA, 2002) or in the
HEAST (U.S. EPA, 1997a). Although mercuric sulfide is not included on IRIS, elemental
mercury and mercuric chloride are listed (U.S. EPA, 2001). IRIS reports an RfD of 0.0003
mg/kg-day for mercuric chloride based on immuno-glomerulonephritis in rats exposed by oral
gavage to mercuric chloride. The source document for this assessment was a Drinking Water
Criteria Document for Inorganic Mercury (U.S. EPA, 1988). This RfD value is reported for
inorganic mercury in the Drinking Water Standards and Health Advisories list; however, no
drinking water standards or health advisories have been established specifically for mercuric
sulfide (U.S. EPA, 2000). An RfD for elemental mercury is not available on IRIS (U.S. EPA,
2001). ATSDR (1999) derived acute and intermediate-duration oral MRLs of 0.007 and 0.002
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mg mercury/kg-day, respectively, based on effects in rats exposed to mercuric chloride by oral
gavage; however no MRLs were derived based on exposures to mercuric sulfide.
The following sources were also consulted for relevant information: CARA list (U.S.
EPA, 1991, 1994), Mercury Study Report to Congress (U.S. EPA, 1997b), Health Issue
Assessment Document for Mercury (U.S. EPA, 1984a), Health Effects Assessment (HEA) for
Mercury (U.S. EPA, 1984b), NTP (2001), IARC (1993, 2001), and WHO (WHO, 1991).
Computer searches of TOXLINE (1965-1993), TOXLIT (1965-1993), NAPRALERT (through
1993), CHEM ID, RTECS, HSDB, MBASE (1974-1993), and TSCATS were conducted in 1993.
Update searches of the following databases were conducted from 1993 to August 2001 for
relevant studies: TOXLINE, MEDLINE, TSCATS, GENETOX, HSDB, CANCERLIT, CCRIS,
RTECS, EMIC/EMICBACK and DART/ETICBACK.
REVIEW OF PERTINENT LITERATURE
The toxicity of mercuric salts appears to be related to cationic mercury (Hg2+), while
solubility and tissue distribution is dependent on the valency state and anionic component of the
mercuric compound (Goyer, 1996). Distribution data from parallel experiments with mercuric
chloride and mercuric sulfide suggest that mercury, administered as mercuric sulfide is less
absorbed than when given as mercuric chloride (Ryan et al., 1991; Sin et al., 1983). For these
reasons, mercuric chloride is regarded as being more toxic than mercuric sulfide. Irrespective of
the route of exposure, the kidney is the critical organ of injury after exposure to mercuric chloride
(Goyer, 1996). High doses of mercuric chloride are directly toxic to renal tubular lining cells,
while chronic low-dose exposure may induce an immunologic glomerular disease (Goyer, 1996;
Henry et al., 1988). Pharmacokinetic studies suggested that once mercuric sulfide has been
absorbed, mercury tends to accumulate in the kidney, liver, and brain (Ryan et al., 1991; Sin et
al., 1990; Yeoh et al., 1986, 1989). These data suggest that exposure to mercuric sulfide may
cause renal effects similar to those observed with mercuric chloride exposure; however, there are
no experimental data to support this contention.
Human Studies
The only information regarding the toxic effects of mercuric sulfide in humans comes
from case studies of patients (1 adult and 1 child) who ingested patent medicines containing both
mercuric sulfide and mercurous chloride (Hg2Cl2) (Kang-Yum and Oransky, 1992). Drooling,
dysphagia, irregular arm movements, impaired gait, and convulsions were effects noted
following ingestion. The study provided limited exposure data. Blood mercury levels of 39-
2800 |-ig/L in 24 hr urine were reported. Definitive conclusions regarding the connection
between these effects and exposure to mercuric sulfide in these patients cannot be made due to
concurrent exposure to multiple mercury compounds.
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Animal Studies
Data from a pharmacokinetic study demonstrated that exposure to mercuric sulfide or
mercuric chloride resulted in a greater accumulation of mercury in the kidneys than in the liver or
the brain (Ryan et al., 1991). In this study, groups of 3-9 female Swiss albino mice received a
single oral dose of 6 or 324 mg mercury/kg body weight as mercuric sulfide or a single oral dose
of 0.6 or 6 mg mercury/kg body weight as mercuric chloride in distilled water. At 24 hours, the
mice were sacrificed and tissue samples were analyzed for mercury. Greater concentrations of
mercury were recovered in blood, brain, liver, and kidneys in mercuric chloride-treated mice than
in mercuric sulfide-treated mice and in controls; this included comparison of the low dose of
mercuric chloride with the high dose of mercuric sulfide.
In another animal study, groups of 6 young adult female Swiss albino mice received doses
of 6 mg mercury/kg body weight as mercuric chloride or mercuric sulfide once a day for 10 days
via oral gavage (Sin et al., 1990). A significantly higher (p<0.05) concentration of mercury
accumulated in the liver, kidney, and brain of mercuric chloride-treated mice than in mercuric
sulfide-treated mice. In both mercuric chloride- and sulfide-treated groups, liver glutathione
(GSH) content was slightly, but not significantly lower than controls; whereas kidney GSH
content in mercuric chloride-treated mice, but not mercuric sulfide-treated mice, was
significantly higher than controls. In mercuric chloride-treated mice, brain GSH content was
slightly, but not significantly higher than controls, while a level comparable to controls was
measured in mercuric sulfide-treated mice. Because GSH is known to be involved in the
metabolism and detoxification of endogenous and exogenous substances, plasma concentrations
of thyroid hormones (T4 and T3) were measured. Plasma thyroid hormone T4 and T3 levels were
significantly lower (p<0.05) in mercuric chloride-treated mice than in the controls, whereas only
the T3 level was significantly reduced in mercuric sulfide-treated mice. A previous study by Sin
et al. (1989), demonstrated that a significantly (p<0.01) greater concentration of mercury was
recovered in the kidneys of mercuric chloride-treated mice than in the mercuric sulfide-treated
mice and the concentrations of mercury at 3, 6, 24 and 72 h after treatment in the kidney were
greater than in the liver. In this study, groups of 4 adult female Swiss albino mice were given 6
or 324 mg mercury/kg-day for 4 days by oral gavage as mercuric sulfide or 6 mg mercury/kg-day
as mercuric chloride. Renal GSH levels were also significantly (p<0.01) elevated in mercuric
chloride-fed mice, as well as in mice fed only the highest dose of mercuric sulfide.
Revis et al. (1990) reported that mice absorbed 0.4% and 2.1% of a single dose of
mercuric sulfide and mercuric chloride, respectively. A single dose of 0.3 mL of a slurry
containing 1E-5 distintegrations per minute (dpm) of 203mercuric chloride or 203mercuric sulfide
was administered by oral gavage to groups of 5 male mice. Fecal samples were collected for 10
days and the mice were then sacrificed and the intestinal tract removed. The amount of
radioactive mercury absorbed was calculated as the difference between the amount intubated and
the amount measured in the feces and intestinal tract. However, there was no account of mercury
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in other tissues, or biliary excretion, a known homeostatic mechanism for Hg (Goyer, 1996). The
interpretation of the authors that 0.4% and 2.1% of mercuric sulfide and mercuric chloride,
respectively, was absorbed appears to be incorrect for the following reasons. The study design
was inappropriate for determining absorption of a chemical such as mercury, some of which may
be distributed to the intestinal mucosa or eliminated by the biliary route and excreted into the
feces following absorption (ATSDR, 1999; U.S. EPA, 1988; WHO, 1991). In addition, the data
do not show significant differences attributable to absorption between compounds. For mercuric
sulfide, for example, the total mercury intubated was 336,580 ± 39,304 dpm (mean ± SD), and
the total mercury in feces and intestinal tract was 335,276 ± 46,498 dpm. From this set of values
the 0.4% absorption was calculated. However, because the standard deviations are greater than
10% of the mean values, a 0.4% difference between means is statistically meaningless. The same
argument applies to the absorption fraction calculated from mercuric chloride measurements.
For mercuric chloride, the total mercury intubated was 441,220 ± 68,185 dpm and the total
mercury in feces and intestinal tract was 432,915 ± 49,113 dpm. These results indicate that not
only was there no meaningful difference between the sulfide and chloride, but that the data
provide no evidence of absorption of either salt, as differences between 0.4%, 2.1 % and 0% are
not statistically significant.
Mice were treated with either 0.1 or 1.0 g mercuric sulfide/kg-day or 0.2, 2.0 or 10 mg
methyl-mercury (MeHg)/kg-day by gastric gavage for 7 consecutive days (Chuu et al., 2001a).
Analysis of auditory brainstem response (ABR) indicated that significant elevation of the
physiological hearing threshold, as well as significant prolongation of interwave latency I-V, was
observed for MeHg (2.0 and 0.2 mg/kg-day) or the high-dose mercuric sulfide-treated mice.
Further, both MeHg- and mercuric sulfide-treated animals demonstrated a significant
prolongation of interwave latency I-V that increased with an increasing mean blood-Hg level.
The oto-neurotoxicity of MeHg (2.0 mg/kg-day) persisted to at least 11 weeks subsequent to the
cessation of its administration. The toxic effect of mercuric sulfide, however, disappeared
completely 5 weeks subsequent to the cessation of its administration. These results suggest a
correlation between the Hg-elicited hearing dysfunction and the availability of mercury in brain
tissue. Both inhibition of Na+/K+-ATPase activity and overproduction of nitric oxide in the
brainstem are consistent with an analysis of the physiological hearing threshold and latencies of
ABR waveform at all time points throughout the experimental process. The authors proposed
that high-dose mercuric sulfide or MeHg intoxication is associated with a decrease in functional
Na+/K+-ATPase activity in the brainstem of affected animals, presumably arising via excessive
nitric oxide production, and suggesting that brainstem damage may play a role in mercury-
induced hearing loss. However, in another study in which nitric oxide synthase (NOS) activity in
rat brain homogenates was monitored in the presence and absence of five mercury salts, all five
salts inhibited NOS with sensitivities in the following order: MeHg > mercuric nitrate> mercuric
iodide > mercuric oxide >mercuric chloride (Desaiah and Roa, 1994).
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Chuu et al. (2001b) assessed the neurobehavioral toxicities of three mercurial
compounds, MeHg, mercuric sulfide and cinnabar (naturally occurring mercuric sulfide). These
compounds were administered intraperitoneally (MeHg, 2 mg/ kg-day) or orally (mercuric sulfide
and cinnabar, 1.0 g/kg-day) to male rats for 13 consecutive days with assays conducted during or
after discontinuous administration at 1 h, 2, 8 and 33 weeks. Neurotoxicity was assessed based
on the active avoidance response and locomotor activity. The results obtained showed that
MeHg and cinnabar prominently and irreversibly caused a decrease in body weight, prolongation
of latency for escape from electric shock, a decrease in the percentage for the conditioned
avoidance response (CAR) to electric shock, impairment of spontaneous locomotion, and
inhibition of Na+/K+-ATPase activity of the cerebral cortex. Mercuric sulfide reversibly inhibited
spontaneous locomotion and Na+/K+-ATPase activity, and significantly decreased the latency of
escape from electric shock during the administration period, which lasted for 33 weeks after
discontinuous administration. Pretreatment with arecoline (a cholinergic receptor agonist) but
not fipexide (a dopaminergic receptor agonist) significantly shortened the prolonged latency for
escape caused by MeHg and cinnabar, suggesting that the deficit in the active avoidance response
was perhaps, at least in part, mediated by the dysfunction of the cholinergic rather than the
dopaminergic system. Determination of the Hg levels of the whole blood and cerebral cortex
revealed that the tissue mercury content was highly correlated with the degree of neurobehavioral
toxicity of these Hg compounds. These findings suggest that insoluble mercuric sulfide and
cinnabar can be absorbed from the G-I tract and distributed to the brain. The possibility that
contamination due to other minerals in the cinnabar was responsible for the greater neurotoxic
effects compared to mercuric sulfide was to be investigated in future studies.
The effects of mercury on renal and hepatic UDP-glucuronyltransferase (UDPGT)
activity were studied in mice (Tan et al., 1990). Young adult female Swiss-mice were
administered 6 mg Hg2+/kg-day as mercuric chloride or mercuric sulfide orally for 10 days. They
were killed 24 hours after the last dose and the livers and kidneys were removed and weighed
and assayed for mercury and UDPGT. Renal and hepatic mercury concentrations and UDPGT
activity in mercuric sulfide-treated mice were not significantly different from those of the
controls; however they were significantly increased in mice given mercuric chloride. The
maximum velocities of glucuronidation were significantly increased in mercuric chloride-treated
mice. The authors concluded that the increase in renal UDPGT activity induced by mercuric
chloride appears to be associated with increased deposition of mercury in renal tissue. The
biological significance of the increase in renal UDPGT activity is unknown. The lack of an
effect of mercuric sulfide on renal UDPGT may reflect poor absorption due to its low solubility.
In one study, groups of 20 young female Swiss albino mice were given a dose of 0 or 6 |ig
Hg2+/g body weight (7 mg mercuric sulfide/kg body weight) in distilled water once a day for 4
weeks by oral gavage (Sin and Teh, 1992). Five mice from each group were sacrificed at 1, 2, 3,
and 4 week intervals after the last treatment. Mercuric sulfide caused a decrease in plasma T3
and T4 levels when data were compared with controls. The decrease in T4 levels was statistically
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significant (p<0.05) at weeks 1 and 4. Body weights of the test group were comparable to those
of the control group at the various time intervals. GSH levels in the kidney and liver from
mercuric sulfide-treated mice were not significantly different from the controls. Despite this,
GSH levels in the brain of mercuric sulfide-treated mice were significantly elevated at week 2
(p<0.05) and week 3 (p<0.01). Analysis of kidney, liver, and brain tissues revealed very low (not
statistically significantly elevated) levels of mercury. The authors proposed that although low
levels of mercuric sulfide were absorbed, this small quantity of mercuric sulfide might interfere
with the normal activities of thyroidal cells or the hypothalamus-pituitary axis.
In another study, groups of 6-12 female Swiss albino mice were fed water containing 0 or
100 ppm of mercuric sulfide (0.23 mg Hg2+/kg-day) or mercuric chloride for 55 days (Ryan et al.,
1991). Mercuric chloride-fed mice showed significantly (p<0.05) higher mercury levels in the
brain, lymphoidal tissue, liver, and spleen as compared to both the control and the mercuric
sulfide-fed mice. The mercury content of these organs and tissues from mercuric sulfide-treated
mice were comparable to controls. At 50 days, the antibody production of mercuric sulfide-fed
mice in response to sheep red blood cells (SRBC) was significantly (p<0.05) enhanced compared
to both control and the mercuric chloride-fed mice. Mercuric sulfide-fed mice also had
significantly (p<0.05) higher white blood cell (WBC) counts compared to other treatment groups.
However, RBC, hemoglobin, body weight, and food consumption determinations were
comparable between the different treatment groups.
A chronic oral exposure study (Revis et al., 1989) was located that examined the effects
of soil contaminated with mercury. However, in addition to mercury, the soil was contaminated
with other metals. In this study, 30 groups of 40 male and 40 female Swiss mice received diets
containing soil contaminated with selenium, zinc, arsenic, lead, cadmium, and mercury for 6, 12,
or 20 months. The authors of this study did not report the use of a control group. The metals-
contaminated soil and sediment were obtained from 30 different sites and added individually to
Purina mouse chow to give a total concentration of 5% soil or sediment per diet. The mercury
compound distribution of soil samples consisted of 88% mercuric sulfide, 7% elemental mercury,
and 0.01% organic mercury. The concentration of mercury in soil ranged from 0.59-1799 ppm.
The investigators measured the daily intake of metals-contaminated soil and determined that
male mice received mercury doses in the range of 0.11-392 |ig Hg2+/day and that female mice
received 0.07-282 |j,g Hg2+/day. Five to 10 animals were sacrificed at 6, 12, or 20 months and a
gross necropsy and histopathological examination of the kidneys were performed. Body weights
were determined and a swim test was used to examine neurological effects. Data showed that the
experimental diets did not affect mortality, the growth of the mice, or liver and kidney weights.
Exposure to metals-contaminated soil appeared to have caused only minor proximal tubular
lesions in the kidney. However, because no controls were used in this study, it is not known if
proximal tubule lesions were treatment-related. Metals-contaminated soil did not appear to cause
neurological effects, as determined by the swim test. However, the authors recognized that the
swim test is not capable of detecting subtle neurological effects.
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In a related experiment, developmental toxicity of the metals-contaminated soil was
assessed (Revis et al, 1989). Three pairs of Swiss mice from the above study exposed for 6
months were time-mated. The litter size was determined at 24 and 96 hours postdelivery.
Exposure had no effect on litter size. Changes in the number of digits of the hand and foot,
apparent neurological effects, and cleft palate were not observed in offspring from soil-exposed
dams. As noted above, there were no controls.
No conclusions regarding the connection between effects or lack of effects noted and
exposure to mercuric sulfide can be made from these chronic studies (Revis et al., 1989) due to
concurrent exposure to multiple metal compounds.
Other Studies
Mercuric chloride was found to elicit an autoantibody response that predominantly targets
fibrillarin, a protein component of many small nucleolar ribonucleoproteins particles (Pollard et
al., 1997). Addition of mercuric chloride to isolated rat liver nuclei resulted in aberrant SDS-
PAGE migration of fibrillarin, but not other nuclear autoantigens. Interaction of mercury with
the two cysteines in the fibrillarin sequence was suggested by the differential sensitivity of the
mercuric chloride-induced modification of fibrillarin to 2-methoxyethanol, iodoacetamide, and
hydrogen peroxide, and confirmed by mutation of the cysteines to alanines, which abolished the
aberrant migration of fibrillarin in the presence of mercuric chloride. Immunoprecipitation by
anti-fibrillarin autoantibodies suggested that unmodified fibrillarin is a B cell antigen, whereas
mercury-modified fibrillarin is the source of T cell antigenicity. These observations suggest a
plausible mechanism of toxicity for mercury-induced immunological effects (immuno-
glomerulonephritis) in rats orally gavaged with mercuric chloride (Andres, 1984).
PROVISIONAL RfD FOR MERCURIC SULFIDE
While altered plasma T4 levels and brain GSH levels were measured in mice treated by
oral gavage with mercuric sulfide (Sin and Teh, 1992), the mechanisms and significance of the
alterations remain unknown, and therefore these data are inadequate bases for derivation of a
p-RfD for mercuric sulfide. In the study by Ryan et al., (1991), the significance of the elevated
WBC count in relation to mercuric sulfide exposure is unknown, and it also not known whether
the heightened WBC count is responsible for the increased antibody production. As stated
previously, no conclusions regarding the toxicity of mercuric sulfide can be made from the study
by Revis et al. (1989) due to concurrent exposure to multiple metal compounds. The lack of data
in humans and of adequate subchronic or chronic oral data in animals precludes derivation of a
provisional RfD for mercuric sulfide.
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Since data are inadequate for mercuric sulfide for derivation of a p-RfD, consideration
was given to the similarity of mercuric sulfide to other inorganic mercury salts such that a p-RfD
might be derived based on common properties of inorganic species, or by analogy to another
inorganic mercury salt, such as mercuric chloride. Data from several animal studies
demonstrated that mercuric chloride is a more bioavailable salt than mercuric sulfide (U.S. EPA,
1993). Additional animal studies have also demonstrated that oral administration of mercuric
chloride resulted in higher concentrations of mercury in the kidney than when mercuric sulfide
was administered (Sin et al., 1983, 1989, 1990). These data suggest that a larger oral dose of
mercuric sulfide compared to mercuric chloride may be required to produce a similar toxic effect
in the kidney. Therefore, based on the limited available pharmacokinetic data for mercuric
sulfide, the RfD for mercuric chloride (0.0003 mg/kg-day) could be considered protective for
mercuric sulfide. It is likely that the actual RfD for mercuric sulfide would be higher by a factor
of at least 10 when compared to that of mercuric chloride, based on their relative bioavailability.
REFERENCES
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Pollard, K.M., D.K. Lee, C.A. Casiano et al. 1997. The autoimmunity-inducing xenobiotic
mercury interacts with the autoantigen fibrillarin and modifies its molecular and antigenic
properties. J. Immunol. 158: 3521-8.
Revis, N., G. Holdsworth, G. Bingham, A. King and J. Elmore. 1989. An assessment of health
risk associated with mercury in soil and sediment from East ForK Poplar Creek, Oak Ridge,
Tennessee. Oak Ridge Research Institute. Final Report, p. 1-58.
Revis, N.W., T.R. Osborne, G. Holdsworth and C. Hadden. 1990. Mercury in Soil: A method
for assessing acceptable limits. Arch. Environ. Contam. Toxicol. 19: 221-226.
Ryan, D.M., Y.M. Sin and M.K. Wong. 1991. Uptake, distribution and immunotoxicological
effects of mercury in mice. Environ. Monit. Assess. 19: 507-517.
Sin, Y.M., W.F. Lim and M.K. Wong. 1983. Uptake and distribution of mercury in mice from
ingesting soluble and insoluble mercury compounds. Bull Environ. Contam. Toxicol. 31: 605-
612.
Sin, Y.M., W.F. Teh and M.K. Wong. 1989. Absorption of mercuric chloride and mercuric
sulfide and their possible effects on tissue glutathione in mice. Bull. Environ. Contam. Toxicol.
42: 307-314.
Sin, Y.M., W.F. Teh, M.K. Wong et al. 1990. Effect of mercury on glutathione and thyroid
hormones. Bull. Environ. Contam. Toxicol. 42: 616-622.
10

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09-25-02
Sin, Y.M., W.F. The, and M.K. Wong. 1992. Effect of long-term uptake of mercuric sulfide on
thyroid hormones and glutathione in mice. Bull. Contam. Toxicol. 49: 847-854.
Tan, T.M.C., Y.M. Sin and K.P. Wong. 1990. Mercury-induced UDPglucuronyltransferase
(UDPGT) activity in mouse kidney. Toxicology. 64:81-87.
U.S. EPA. 1984a. Mercury Health Effects Update. Health Issue Assessment. Prepared by the
Office of Health and Environmental Assessment, Research Triangle Park, NC, for the Office of
Air Quality Planning and Standards, Washington, DC.
U.S. EPA. 1984b. Health Effects Assessment (HEA) for Mercury. Prepared by the Office of
Health and Environmental Assessment Office, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1988. Drinking Water Criteria Document for Inorganic Mercury. Prepared by the
Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH, for the Office of Drinking Water, Washington, DC.
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA), Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA), Office of Health and
Environmental Assessment, Washington, DC. December.
U.S. EPA. 1993. Memorandum to Stan Smucker, U.S. EPA, Region IX from Joan Dollarhide,
Superfund Technical Support Center, June 17, 1993. Risk Assessment Issue Paper for: Oral
absorption of mercuric sulfide (Sulphide).
U.S. EPA. 1997a. Health Effects Assessment Summary Tables (HEAST). FY-1997 Update.
Prepared by the Office of Research and Development, National Center for Environmental
Assessment, Cincinnati, OH for the Office of Emergency and Remedial Response, Washington,
DC. July. EPA/540/R/97/036. NTIS PB 97-921199.
U.S. EPA. 1997b. Mercury Study Report to Congress. Volume V: Health Effects of Mercury
and Mercury Compounds. Office of Air Quality Planning and Standards and Office of Research
and Development. December. EPA/452/R/97/007.
U.S. EPA. 2000. Drinking Water Regulations and Health Advisories. Office of Water,
Washington, DC. Examined September 7, 2001. Online, www.epa.gov/ost/drinking/standards/
11

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09-25-02
U.S. EPA. 2002. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Examined
September 7, 2001. Online, www.epa.gov/iris
WHO (World Health Organization). 1991. Environmental Health Criteria. 118: Inorganic
Mercury. International Programme on Chemical Safety, Geneva, Switzerland. Online.
www.inchem.org/documents/ehc/ehc/EHC 118.HTM
Yeoh, T.S., A.S. Lee and H.S. Lee. 1986. Absorption of mercuric sulfide following oral
administration in mice. Toxicology. 41: 107-111.
Yeoh, T.S., H.S. Lee and A.S. Lee. 1989. Gastrointestinal absorption of mercury following oral
administration of cinnabar in a traditional Chinese medicine. Asia Pacific J. Pharmacol.
4: 69-73.
12

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09-25-02
Provisional Peer Reviewed Toxicity Values for
Mercuric sulfide
(CASRN 1344-48-5)
Derivation of a Chronic Inhalation RfC
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
i.v.	intravenous
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
1

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MTD
maximum tolerated dose
MTL
median threshold limit
NAAQS
National Ambient Air Quality Standards
NOAEL
no-observed-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-observed-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
PBPK
physiologically based pharmacokinetic
PPb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor
Hg
microgram
|j,mol
micromoles
voc
volatile organic compound
11

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09-25-02
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
MERCURIC SULFIDE (CASRN 1344-48-5)
Derivation of a Chronic Inhalation RfC
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3.	Other (peer-reviewed) toxicity values, including:
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because science and available information evolve, PPRTVs are initially derived with a
three-year life-cycle. However, EPA Regions or the EPA Headquarters Superfund Program
sometimes request that a frequently used PPRTV be reassessed. Once an IRIS value for a
specific chemical becomes available for Agency review, the analogous PPRTV for that same
chemical is retired. It should also be noted that some PPRTV manuscripts conclude that a
PPRTV cannot be derived based on inadequate data.
1

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09-25-02
Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
An RfC for mercuric sulfide (HgS) is not available on IRIS (U.S. EPA, 2002) or in the
HEAST (U.S. EPA, 1997a). Although mercuric sulfide is not included on IRIS, elemental
mercury and mercuric chloride are listed (U.S. EPA, 2002). IRIS reports an RfC of 0.3 |_ig Hg/m3
for elemental mercury based on exposures in humans to metallic mercury vapor. An RfC for
mercuric chloride is not available on IRIS (U.S. EPA, 2002). ATSDR (1999) derived a chronic
inhalation MRL of 0.2 |ig Hg/m3 for metallic mercury; however no MRLs were derived based on
exposures to mercuric sulfide. ACGIH (2001), NIOSH (2001), and OSHA (2001) have not
assessed the toxicity of mercuric sulfide; however these agencies report exposure limits for
inorganic mercury based on studies of mercuric chloride.
2

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09-25-02
The following sources were also consulted for relevant information: CARA list (U.S.
EPA, 1991, 1994), Mercury Study Report to Congress (U.S. EPA, 1997b), Health Issue
Assessment Document for Mercury (U.S. EPA, 1984a), Health Effects Assessment (HEA) for
Mercury (U.S. EPA, 1984b), NTP (2001), IARC (1993, 2001), and WHO (1991). Computer
searches of TOXLINE (1965-1993), TOXLIT (1965-1993), NAPRALERT (through 1993),
CHEM ID, RTECS, HSDB, MBASE (1974-1993), and TSCATS were conducted in 1993.
Update searches of the following databases were conducted from 1993 to August 2001 for
relevant studies: TOXLINE, MEDLINE, TSCATS, GENETOX, HSDB, CANCERLIT, CCRIS,
RTECS, EMIC/EMICBACK and DART/ETICBACK.
REVIEW OF PERTINENT LITERATURE
Human Studies
While data exist on inhalation exposure to metallic mercury vapor, the available reviews
(U.S. EPA, 1984a,b, 1997b; AT SDR, 1999; IARC, 1993; WHO, 1991) found no toxicity studies
of mercuric sulfide or other inorganic mercury salts in humans following inhalation exposure.
The literature search identified no new studies regarding toxicity of mercuric sulfide in humans
following inhalation exposure.
Animal Studies
The available reviews (U.S. EPA, 1984a,b, 1997b; ATSDR, 1999; IARC, 1993; WHO,
1991) found no toxicity studies of mercuric sulfide in animals following inhalation exposure.
The literature search identified no new studies regarding the toxicity of mercuric sulfide in
animals following inhalation exposure.
FEASIBILITY OF DERIVING A PROVISIONAL RfC FOR MERCURIC SULFIDE
The lack of data in humans and in animals following inhalation exposure precludes
derivation of a provisional RfC for mercuric sulfide.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 2001. TLVs® and
BEIs®: Threshold Limit Values for Chemical Substances and Physical Agents, Biological
Exposure Indices. Cincinnati, OH.
3

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09-25-02
ATSDR (Agency for Toxic Substances and Disease Registry). 1999. Toxicological Profile for
Mercury. U.S. Department of Health and Human Services, Public Health Service. March 1999.
Online, www.atsdr.cdc.gov/toxprofiles/tp46.html
I ARC (International Agency for Research on Cancer). 1993. IARC Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals to Humans. Beryllium, Cadmium, Mercury,
and Exposures in the Glass Manufacturing Industry Chemical, Environmental and Experimental
Data, Vol. 58. p. 239.
IARC (International Agency for Research on Cancer). 2001. IARC Monograph Series.
Examined September 11, 2001. Agents and Summary Evaluations. Online.
http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html
NIOSH (National Institute for Occupational Safety and Health). 2001. Online NIOSH Pocket
Guide to Chemical Hazards. Index by CASRN. Examined September 11, 2001. Online.
www.cdc.gov/niosh/npg/npgdcas.html
NTP (National Toxicology Program). 2001. NTP Testing Information and Study Results. NTP
Management Status Report. Examined September 11, 2001. Online.
http://ntp-server.niehs.nih.gov/cgi/iH Indexes/MSR/iH MSR Frames.html
OSHA (Occupational Safety and Health Administration). 2001. OSHA Standard 1915.1000 for
Air Contaminants. Part Z, Toxic and Hazardous Substances. Examined September 11, 2001.
Online. www.osha-slc.gov/OshStd data/1915 1000.html
U.S. EPA. 1984a. Mercury Health Effects Update. Health Issue Assessment. Prepared by the
Office of Health and Environmental Assessment, Research Triangle Park, NC, for the Office of
Air Quality Planning and Standards, Washington, DC.
U.S. EPA. 1984b. Health Effects Assessment (HEA) for Mercury. Prepared by the Office of
Health and Environmental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH, for the Office of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA), Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA), Office of Health and
Environmental Assessment, Washington, DC. December.
4

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09-25-02
U.S. EPA. 1997. Health Effects Assessment Summary Tables (HEAST). FY-1997 Update.
Prepared by the Office of Research and Development, National Center for Environmental
Assessment, Cincinnati, OH, for the Office of Emergency and Remedial Response, Washington,
DC. July. EPA/540/R/97/036. NTIS PB 97-921199.
U.S. EPA. 1997b. Mercury Study Report to Congress. Volume V: Health Effects of Mercury
and Mercury Compounds. Office of Air Quality Planning and Standards and Office of Research
and Development. December. EPA-452/R/97/007.
U.S. EPA. 2002. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Examined
September 7, 2001. Online, www.epa.gov/iris
WHO (World Health Organization). 1991. Environmental Health Criteria. 118: Inorganic
Mercury. International Programme on Chemical Safety, Geneva, Switzerland. Online.
www.inchem.org/documents/ehc/ehc/EHC 118.HTM
5

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09-25-02
Provisional Peer Reviewed Toxicity Values for
Mercuric sulfide
(CASRN 1344-48-5)
Derivation of a Carcinogenicity Assessment
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
i.v.	intravenous
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
1

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MTD
maximum tolerated dose
MTL
median threshold limit
NAAQS
National Ambient Air Quality Standards
NOAEL
no-observed-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-observed-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
PBPK
physiologically based pharmacokinetic
PPb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor
Hg
microgram
|j,mol
micromoles
voc
volatile organic compound
11

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09-25-02
PROVISIONAL PEER REVIEWED TOXICITY VALUES
MERCURIC SULFIDE (CASRN 1344-48-5)
Derivation of a Carcinogenicity Assessment
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3.	Other (peer-reviewed) toxicity values, including:
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because science and available information evolve, PPRTVs are initially derived with a
three-year life-cycle. However, EPA Regions or the EPA Headquarters Superfund Program
sometimes request that a frequently used PPRTV be reassessed. Once an IRIS value for a
specific chemical becomes available for Agency review, the analogous PPRTV for that same
chemical is retired. It should also be noted that some PPRTV manuscripts conclude that a
PPRTV cannot be derived based on inadequate data.
1

-------
09-25-02
Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
A cancer assessment for mercuric sulfide (HgS) is not available on IRIS (U.S. EPA,
2002) or in the HEAST (U.S. EPA, 1997a). Although mercuric sulfide is not included on IRIS,
elemental mercury and mercuric chloride are listed (U.S. EPA, 2002). IRIS classifies elemental
mercury in cancer weight-of-evidence Group D (not classifiable as to human carcinogenicity)
based on inadequate human and animal data, and mercuric chloride in Group C (possible human
carcinogen) based on limited animal data showing equivocal evidence for treatment-related
tumors in the forestomach, thyroid and kidney in some rodent studies. Quantitative estimates of
cancer risk were not derived for mercuric chloride (U.S. EPA, 2002). A Group D classification
is reported for inorganic mercury in the Drinking Water Standards and Health Advisories list
(U.S. EPA, 2001). Neither IARC (1993) nor ACGIH (2001) have assessed the carcinogenicity of
mercuric sulfide. Based on inadequate evidence in humans for the carcinogenicity of mercury
2

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09-25-02
and mercury compounds, inadequate evidence in experimental animals for the carcinogenicity of
metallic mercury, and limited evidence in experimental animals for the carcinogenicity of
mercuric chloride, IARC (1993) has determined that metallic mercury and inorganic mercury
compounds are not classifiable as to their carcinogenicity to humans (Group 3). ACGIH (2001)
has assigned elemental and inorganic forms of mercury to carcinogenicity category A4-not
classifiable as a human carcinogen.
The following sources were also consulted for relevant information: CARA list (U.S.
EPA, 1991, 1994), Mercury Study Report to Congress (U.S. EPA, 1997b), Drinking Water
Criteria Document for Inorganic Mercury (U.S. EPA, 1988), Health Issue Assessment Document
for Mercury (U.S. EPA, 1984a), Health Effects Assessment (HEA) for Mercury (U.S. EPA,
1984b), Toxicological Profile for Mercury (ATSDR, 1999), NTP (2001), and WHO (WHO,
1991). Computer searches of TOXLINE (1965-1993), TOXLIT (1965-1993), NAPRALERT
(through 1993), CHEM ID, RTECS, HSDB, MBASE (1974-1993), and TSCATS were
conducted in 1993. Update searches of the following databases were conducted from 1993 to
August 2001 for relevant studies: TOXLINE, MEDLINE, TSCATS, GENETOX, HSDB,
CANCERLIT, CCRIS, RTECS, EMIC/EMICBACK and DART/ETICBACK.
REVIEW OF PERTINENT LITERATURE
Human Studies
The available reviews (U.S. EPA, 1984a,b, 1988, 1997b; ATSDR, 1999; IARC, 1993;
WHO, 1991) found no studies regarding the carcinogenicity of mercuric sulfide in humans. The
literature search identified no new studies regarding the carcinogenicity of mercuric sulfide in
humans.
Animal Studies
While limited data exist for the carcinogenicity of mercuric chloride in animals (U.S.
EPA, 1997b, 2001a), the available reviews (U.S. EPA, 1984a,b, 1988, 1997b; ATSDR, 1999;
IARC, 1993; WHO, 1991) found no studies regarding the carcinogenicity of mercuric sulfide in
animals. The literature search identified no new studies regarding the carcinogenicity of
mercuric sulfide in animals.
Other Studies
While data for genotoxicity of elemental mercury and mercuric chloride exist, no studies
were located regarding the genotoxicity of mercuric sulfide.
3

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09-25-02
PROVISIONAL WEIGHT-OF-EVIDENCE CLASSIFICATION
No data were located regarding the carcinogenicity of mercuric sulfide in humans or
animals. Following the U.S. EPA (1999) proposed guidelines for carcinogen risk assessment, the
data for mercuric sulfide are inadequate for an assessment of human carcinogenic potential.
QUANTITATIVE ESTIMATES OF CARCINOGENIC RISK
The lack of cancer data precludes derivation of a provisional oral slope factor or a
provisional inhalation unit risk for mercuric sulfide.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 2001. TLVs® and
BEIs®: Threshold Limit Values for Chemical Substances and Physical Agents, Biological
Exposure Indices. ACGIH, Cincinnati, OH.
ATSDR (Agency for Toxicological Substances Disease Registry). 1999. Toxicological Profile
for Mercury. U.S. Department of Health and Human Services, Public Health Service. March,
1999. Online, www.atsdr.cdc.gov/toxprofiles/tp46.html
I ARC (International Agency for Research on Cancer). 1993. IARC Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals to Humans. Beryllium, Cadmium, Mercury,
and Exposures in the Glass Manufacturing Industry Chemical, Environmental and Experimental
Data, Vol. 58. p. 239.
NTP (National Toxicology Program). 2001. NTP Testing Information and Study Results. NTP
Management Status Report. Examined September 11, 2001. Online.
http://ntp-server.niehs.nih.gov/cgi/iH Indexes/MSR/iH MSR Frames.html
U.S. EPA. 1984a. Mercury Health Effects Update. Health Issue Assessment. Prepared by the
Office of Health and Environmental Assessment, Research Triangle Park, NC, for the Office of
Air Quality Planning and Standards, Washington, DC.
U.S. EPA. 1984b. Health Effects Assessment (HEA) for Mercury. Prepared by the Office of
Health and Environmental Assessment, Environmental Criteria Assessment Office, Cincinnati,
OH for the Office of Emergency and Remedial Response, Washington, DC.
4

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09-25-02
U.S. EPA. 1988. Drinking Water Criteria Document for Inorganic Mercury. Prepared by the
Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Drinking Water, Washington, DC.
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA), Office of Health and
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